The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity.

By Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, M. Zhong, Hua Yuan, Lin Zhang, Timothy R. Billiar and 5 more. Cell Reports, 2017

838 citations recorded by the source corpus.

Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis. These findings reveal a direct molecular link between TP53 and DPP4 in the control of lipid metabolism and may provide a precision medicine strategy for the treatment of colorectal cancer by induction of ferroptosis.

Subfields: Cancer Research, Molecular Biology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/fa87881ed0993bf71fccd556366f1da446968840

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Citations in the corpus

Targeting p53 pathways: mechanisms, structures and advances in therapy (2023, background): “On the other hand, interaction of p53 with DPP4 promotes nuclear accumulation of DPP4 and blocks plasmamembrane-associated DPP4-dependent lipid peroxidation, thus limiting ferroptosis.(133) The p53-p21 axis may contribute to the inhibition of cysteine deprivation-induced ferroptosis,(134) whereas it”
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 (2018, background): “Additional ferroptosis regulators described so far include: (1) the mevalonate pathway component farnesyldiphosphate farnesyltransferase 1 (FDFT1; best known as SQS) [545]; (2) the transsulfuration pathway enzyme cysteinyl-tRNA synthetase (CARS) [578]; (3) heat shock protein family B (small) member ”
The cell biology of ferroptosis (2024, neutral): “The tumour suppressor protein p53 also seems to be capable of either promoting or inhibiting ferroptosis through various molecular mechanisms, depending on the cell type and even on the nature of the ferroptosis-inducing stimulus 6,117,164,193”